Effective pulmonary mucociliary clearance is dependent upon the respiratory tract fluid. Ion transport by airway epithelia plays a critical role in controlling volume and composition of the respiratory tract fluid, and thus in controlling mucociliary clearance. The overall aim of this proposal is to characterize the mechanisms of airway epithelial ion transport. There are two specific aims. The first goal is to define the cellular mechanisms of ion transport by tracheal epithelium. To gain an understanding of the mechanisms involved, it is necessary to examine the transport processes at the level of the individual cell membranes. This work will be directed at a definition of the electrochemical driving forces for ion movement across each cell membrane, the ionic permeabilities of the membranes, and the development of kinetic, mechanistic descriptions of the membrane transport processes. This approach requires the use of techniques capable of probing the cell interior and of focusing on ion flows across individual cell membranes. In these studies I will use intracellular microelectrode techniques, an equivalent electrical circuit analysis, intracellular ion-selective microelectrodes, and the measurement of radioisotope fluxes to characterize the individual transport mechanisms. The second aim of this proposal is to investigate the abnormalities of airway epithelial ion transport in diseases associated with abnormal mucociliary clearance. Specifically, I will focus on the abnormalities of airway ion transport associated with cystic fibrosis and the inhalaton of cigarette smoke.